{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:34:00Z","timestamp":1791545640993,"version":"4.3.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Fish Physiol Biochem"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s10695-025-01588-7","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:42:15Z","timestamp":1760956935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exemestane induces liver toxicity in zebrafish larvae by upregulating the p53 signaling pathway"],"prefix":"10.1007","volume":"51","author":[{"given":"Weirong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhua","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"1588_CR1","doi-asserted-by":"crossref","unstructured":"AF Sobral, C Amaral, G Correia-da-Silva, et al (2016) Unravelling exemestane: from biology to clinical prospects [J]. J Steroid Biochem Mol Biol.","DOI":"10.1016\/j.jsbmb.2016.03.019"},{"key":"1588_CR2","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2016.49.9.141","author":"R Barakat","year":"2016","unstructured":"Barakat R, Oakley O, Kim H et al (2016) Extra-gonadal sites of estrogen biosynthesis and function. BMB Rep. https:\/\/doi.org\/10.5483\/BMBRep.2016.49.9.141","journal-title":"BMB Rep"},{"key":"1588_CR3","doi-asserted-by":"publisher","unstructured":"BT Palmisano, L Zhu, JM Stafford (2017) Role of estrogens in the regulation of liver lipid metabolism [J]. Adv Exp Med Biol. https:\/\/doi.org\/10.1007\/978-3-319-70178-3_12.","DOI":"10.1007\/978-3-319-70178-3_12"},{"key":"1588_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1223-5","author":"M Charni","year":"2014","unstructured":"Charni M, Rivlin N, Molchadsky A (2014) P53 in liver pathologies\u2014taking the good with the bad. J Mol Med. https:\/\/doi.org\/10.1007\/s00109-014-1223-5","journal-title":"J Mol Med"},{"key":"1588_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc991","author":"P Ch\u00e8ne","year":"2003","unstructured":"Ch\u00e8ne P (2003) Inhibiting the p53\u2013MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer. https:\/\/doi.org\/10.1038\/nrc991","journal-title":"Nat Rev Cancer"},{"key":"1588_CR6","doi-asserted-by":"publisher","unstructured":"D Clemett, HM Lamb (2000) Exemestane: a review of its use in postmenopausal women with advanced breast cancer [J]. Drugs. https:\/\/doi.org\/10.2165\/00003495-200059060-00007","DOI":"10.2165\/00003495-200059060-00007"},{"key":"1588_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017","author":"H Devarbhavi","year":"2023","unstructured":"Devarbhavi H, Asrani SK, Arab JP (2023) Global burden of liver disease: 2023 update. J Hepatol. https:\/\/doi.org\/10.1016\/j.jhep.2023.03.017","journal-title":"J Hepatol"},{"key":"1588_CR8","doi-asserted-by":"publisher","DOI":"10.1080\/21623945.2023.2179334","author":"J Du","year":"2023","unstructured":"Du J, Zhao Li, Kang Q et al (2023) An optimized method for oil red o staining with the salicylic acid ethanol solution. Adipocyte. https:\/\/doi.org\/10.1080\/21623945.2023.2179334","journal-title":"Adipocyte"},{"key":"1588_CR9","doi-asserted-by":"publisher","DOI":"10.2144\/btn-2022-0038","author":"K Dunn","year":"2022","unstructured":"Dunn K, Vashisht A, Hammond-Weinberger DR (2022) Comparative in situ hybridization protocols in zebrafish. Biotechniques. https:\/\/doi.org\/10.2144\/btn-2022-0038","journal-title":"Biotechniques"},{"key":"1588_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(02)00017-9","author":"HA Field","year":"2003","unstructured":"Field HA, Ober EA, Roeser T et al (2003) Formation of the digestive system in zebrafish. I. Liver morphogenesis. Dev Biol. https:\/\/doi.org\/10.1016\/S0012-1606(02)00017-9","journal-title":"Dev Biol"},{"key":"1588_CR11","doi-asserted-by":"publisher","unstructured":"Foglietta Jennifer, Inno Alessandro, de Iuliis Francesca, et al (2016) Cardiotoxicity of aromatase inhibitors in breast cancer patients [J]. Clinical Breast Cancer. https:\/\/doi.org\/10.1016\/j.clbc.2016.07.003.","DOI":"10.1016\/j.clbc.2016.07.003"},{"key":"1588_CR12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803164","author":"PA Francis","year":"2018","unstructured":"Francis PA, Pagani O, Fleming GF et al (2018) Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa1803164","journal-title":"N Engl J Med"},{"key":"1588_CR13","doi-asserted-by":"publisher","unstructured":"Fritzsche Dane, Indorf Amy, Miske Abby, et al (2020) Exemestane induced cholestatic liver injury - a case report [J]. J Oncol Pharm Pract. https:\/\/doi.org\/10.1177\/1078155220957726.","DOI":"10.1177\/1078155220957726"},{"key":"1588_CR14","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-15-0269","author":"ME Gatti-Mays","year":"2016","unstructured":"Gatti-Mays ME, Venzon D, Galbo CE (2016) Exemestane use in postmenopausal women at high risk for invasive breast cancer: evaluating biomarkers of efficacy and safety. Cancer Prev Res. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-15-0269","journal-title":"Cancer Prev Res"},{"key":"1588_CR15","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.08.034","author":"W Goessling","year":"2015","unstructured":"Goessling W, Sadler KC (2015) Zebrafish: an important tool for liver disease research. Gastroenterology. https:\/\/doi.org\/10.1053\/j.gastro.2015.08.034","journal-title":"Gastroenterology"},{"key":"1588_CR16","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12570","author":"T Goto","year":"2017","unstructured":"Goto T, Elbahrawy A, Furuyama K et al (2017) Liver\u2010specific Prox1 inactivation causes hepatic injury and glucose intolerance in mice. FEBS Lett. https:\/\/doi.org\/10.1002\/1873-3468.12570","journal-title":"FEBS Lett"},{"key":"1588_CR17","doi-asserted-by":"publisher","unstructured":"Gut Philipp, Reischauer Sven, Stainier Didier Y. R., et al (2017) Little fish, big data: zebrafish as a model for cardiovascular and metabolic disease [J]. Physiol Rev. https:\/\/doi.org\/10.1152\/physrev.00038.2016.","DOI":"10.1152\/physrev.00038.2016"},{"key":"1588_CR18","unstructured":"G Zucchini, E Geuna, A Milani, et al (2015) Clinical utility of exemestane in the treatment of breast cancer [J]. International journal of women's health."},{"key":"1588_CR19","doi-asserted-by":"publisher","unstructured":"Horzmann Katharine A., Freeman Jennifer L (2018) Making waves: new developments in toxicology with the zebrafish [J]. Toxicological Sciences. https:\/\/doi.org\/10.1093\/toxsci\/kfy044.","DOI":"10.1093\/toxsci\/kfy044"},{"key":"1588_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/nature12111","author":"K Howe","year":"2013","unstructured":"Howe K, Clark MD, Torroja CF (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature. https:\/\/doi.org\/10.1038\/nature12111","journal-title":"Nature"},{"key":"1588_CR21","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29020346","author":"S Janowska","year":"2024","unstructured":"Janowska S, Holota S, Lesyk R et al (2024) Aromatase inhibitors as a promising direction for the search for new anticancer drugs. Molecules. https:\/\/doi.org\/10.3390\/molecules29020346","journal-title":"Molecules"},{"key":"1588_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042032","author":"V Jazbutyte","year":"2012","unstructured":"Jazbutyte V, Stumpner J, Redel A et al (2012) Aromatase inhibition attenuates desflurane-induced preconditioning against acute myocardial infarction in male mouse heart in vivo. PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0042032","journal-title":"PLoS ONE"},{"key":"1588_CR23","doi-asserted-by":"publisher","unstructured":"Jin Qingxia, Hu Yuqing, Gao Yuqi, et al (2023) Hhex and Prox1a synergistically dictate the hepatoblast to hepatocyte differentiation in zebrafish [J]. Biochem Biophys Res Commun. https:\/\/doi.org\/10.1016\/j.bbrc.2023.149182.","DOI":"10.1016\/j.bbrc.2023.149182"},{"key":"1588_CR24","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4031","author":"S Katoch","year":"2020","unstructured":"Katoch S, Patial V (2020) Zebrafish: an emerging model system to study liver diseases and related drug discovery. J Appl Toxicol. https:\/\/doi.org\/10.1002\/jat.4031","journal-title":"J Appl Toxicol"},{"key":"1588_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095005","author":"N Koo","year":"2022","unstructured":"Koo N, Sharma AK, Narayan S (2022) Therapeutics targeting p53-MDM2 interaction to induce cancer cell death. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms23095005","journal-title":"Int J Mol Sci"},{"key":"1588_CR26","doi-asserted-by":"crossref","unstructured":"Linares Victoria, Alonso Virginia, Albina Maria L., et al (2008) Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine [J]. Toxicology.","DOI":"10.1016\/j.tox.2008.11.010"},{"key":"1588_CR27","doi-asserted-by":"publisher","unstructured":"Liu Fasheng, Hu Hongmei, Chen Guilan, et al (2023) Pexidartinib hydrochloride exposure induces developmental toxicity and immunotoxicity in zebrafish embryos via activation of Wnt signaling [J]. Fish & Shellfish Immunology. https:\/\/doi.org\/10.1016\/j.fsi.2023.108849.","DOI":"10.1016\/j.fsi.2023.108849"},{"key":"1588_CR28","doi-asserted-by":"publisher","unstructured":"Liu Juan, Zhang Cen, Wang Jianming, et al (2020) The regulation of ferroptosis by tumor suppressor p53 and its pathway [J]. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21218387.\u00a0","DOI":"10.3390\/ijms21218387"},{"key":"1588_CR29","doi-asserted-by":"publisher","unstructured":"Liu Yanqing, Gu Wei (2021) The complexity of p53-mediated metabolic regulation in tumor suppression [J]. Semin Cancer Biol. https:\/\/doi.org\/10.1016\/j.semcancer.2021.03.01.","DOI":"10.1016\/j.semcancer.2021.03.01"},{"key":"1588_CR30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.01740.x","author":"A Nawathe","year":"2008","unstructured":"Nawathe A, Patwardhan S, Yates D et al (2008) Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG. https:\/\/doi.org\/10.1111\/j.1471-0528.2008.01740.x","journal-title":"BJOG"},{"key":"1588_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.06.009","author":"J Pilic","year":"2024","unstructured":"Pilic J, Gottschalk B, Bourgeois B (2024) Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress. Mol Cell. https:\/\/doi.org\/10.1016\/j.molcel.2024.06.009","journal-title":"Mol Cell"},{"key":"1588_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-9-90","author":"NP Polyzos","year":"2011","unstructured":"Polyzos NP, Fatemi HM, Zavos A et al (2011) Aromatase inhibitors in post-menopausal endometriosis. Reprod Biol Endocrinol. https:\/\/doi.org\/10.1186\/1477-7827-9-90","journal-title":"Reprod Biol Endocrinol"},{"key":"1588_CR33","doi-asserted-by":"crossref","unstructured":"Rosa Jo\u00e3o Gabriel Santos, Lima Carla, Lopes-Ferreira Monica (2022) Zebrafish larvae behavior models as a tool for drug screenings and pre-clinical trials: a review [J]. Int J Mol Sci.","DOI":"10.3390\/ijms23126647"},{"key":"1588_CR34","doi-asserted-by":"publisher","unstructured":"Sadasivam Nanthini, Kim Yu-Ji, Radhakrishnan Kamalakannan, et al (2022) Oxidative stress, genomic integrity, and liver diseases [J]. Molecules. https:\/\/doi.org\/10.3390\/molecules27103159.","DOI":"10.3390\/molecules27103159"},{"key":"1588_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.11.007","author":"D Sharma","year":"2022","unstructured":"Sharma D, Singh M, Rani R (2022) Role of LDH in tumor glycolysis: regulation of LDHA by small molecules for cancer therapeutics. Semin Cancer Biol. https:\/\/doi.org\/10.1016\/j.semcancer.2022.11.007","journal-title":"Semin Cancer Biol"},{"key":"1588_CR36","doi-asserted-by":"crossref","unstructured":"S\u0142opie\u0144 Rados\u0142aw, M\u0119czekalski B\u0142a\u017cej (2016) Aromatase inhibitors in the treatment of endometriosis [J]. Menopausal Review.","DOI":"10.5114\/pm.2016.58773"},{"key":"1588_CR37","unstructured":"Takagi Atsuko, Ikeda Yasuyuki (2013) Genetic diagnosis on hypertriglyceridemia-analysis for LPL gene mutations [J]. Nihon rinsho Japanese journal of clinical medicine."},{"key":"1588_CR38","doi-asserted-by":"publisher","unstructured":"VE Bianchi, E Bresciani, R Meanti, et al (2021) The role of androgens in women\u2019s health and wellbeing [J]. Pharmacol Res. https:\/\/doi.org\/10.1016\/j.phrs.2021.105758.","DOI":"10.1016\/j.phrs.2021.105758"},{"key":"1588_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/nrc864","author":"KH Vousden","year":"2002","unstructured":"Vousden KH, Lu X (2002) Live or let die: the cell\u2019s response to p53. Nat Rev Cancer. https:\/\/doi.org\/10.1038\/nrc864","journal-title":"Nat Rev Cancer"},{"key":"1588_CR40","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-021-01924-2","author":"Y Wang","year":"2022","unstructured":"Wang Y, Jing F, Wang H (2022) Role of exemestane in the treatment of estrogen-receptor-positive breast cancer: a narrative review of recent evidence. Adv Ther. https:\/\/doi.org\/10.1007\/s12325-021-01924-2","journal-title":"Adv Ther"},{"key":"1588_CR41","doi-asserted-by":"crossref","unstructured":"Yang Wang, Ling Xi, He Shijun, et al (2023) PPAR\u03b1\/ACOX1 as a novel target for hepatic lipid metabolism disorders induced by per- and polyfluoroalkyl substances: an integrated approach [J]. Environ Int.","DOI":"10.1016\/j.envint.2023.108138"},{"key":"1588_CR42","doi-asserted-by":"publisher","unstructured":"Ye Qian, Liu Yi, Zhang Guiji, et al (2013) Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K\/AKT\/PDGF axis activation in male mice [J]. Nat Commun. https:\/\/doi.org\/10.1038\/s41467-023-37142-3.","DOI":"10.1038\/s41467-023-37142-3"},{"key":"1588_CR43","doi-asserted-by":"crossref","unstructured":"YM Yu, BH Zhou, YL Yang, et al (2021) Estrogen deficiency aggravates fluoride-induced liver damage and lipid metabolism disorder in rats [J]. Biol Trace Elem Res.","DOI":"10.1007\/s12011-021-02857-1"},{"key":"1588_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/srep15838","author":"H Yuan","year":"2015","unstructured":"Yuan H, Wen B, Liu X (2015) CCAAT\/enhancer-binding protein \u03b1 is required for hepatic outgrowth via the p53 pathway in zebrafish. Sci Rep. https:\/\/doi.org\/10.1038\/srep15838","journal-title":"Sci Rep"},{"key":"1588_CR45","doi-asserted-by":"publisher","unstructured":"Zhang Li, Li Xue, Yuan Qiang, et al (2024) Isavuconazole induces neurodevelopment defects and motor behaviour impairment in zebrafish larvae [J]. Mol Neurobiol. https:\/\/doi.org\/10.1007\/s12035-024-04245-x.","DOI":"10.1007\/s12035-024-04245-x"},{"key":"1588_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117402","author":"M Zhuang","year":"2021","unstructured":"Zhuang M, Achmon Y, Cao Y et al (2021) Distribution of antibiotic resistance genes in the environment. Environ Pollut. https:\/\/doi.org\/10.1016\/j.envpol.2021.117402","journal-title":"Environ Pollut"},{"key":"1588_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.04.010","author":"J Zlatkovi\u0107","year":"2014","unstructured":"Zlatkovi\u0107 J, Todorovi\u0107 N, Tomanovi\u0107 N et al (2014) Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study. Eur J Pharm Sci. https:\/\/doi.org\/10.1016\/j.ejps.2014.04.010","journal-title":"Eur J Pharm Sci"}],"container-title":["Fish Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10695-025-01588-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10695-025-01588-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10695-025-01588-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T09:12:44Z","timestamp":1767172364000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10695-025-01588-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1588"],"URL":"https:\/\/doi.org\/10.1007\/s10695-025-01588-7","relation":{},"ISSN":["0920-1742","1573-5168"],"issn-type":[{"value":"0920-1742","type":"print"},{"value":"1573-5168","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"assertion":[{"value":"4 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study was reviewed and approved by Institutional Animal Care and Use Committee protocols from Jinggangshan University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All the authors have read the manuscript and agreed for its publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"177"}}